The placenta produces a high amount of progesterone, which is absolutely required to maintain a quiescent myometrium and a pregnant uterus. Progesterone production by the placenta is largely unregulated—the placenta produces as much progesterone as the supply of cholesterol and the levels of CYP11A1 and 3β-HSD allow (
Fig. 44.35 ). Notably, placental steroidogenesis differs from that in the adrenal cortex, ovaries, and testis in that cholesterol is transported into the placental mitochondria by a mechanism that is independent of StAR protein. Thus this first step in steroidogenesis is not a regulated rate-limiting step in the placenta as it is in other steroidogenic glands. This means that fetuses with an inactivating mutation in StAR protein will develop lipoid congenital adrenal hyperplasia (see ) and hypogonadism but will have normal progesterone levels produced by their placenta. Progesterone production by the placenta does not require fetal tissue. Consequently, progesterone levels are largely independent of fetal health and cannot be used as a measure of fetal health. Maternal progesterone levels continue to increase throughout pregnancy.
•Fig. 44.35 Productionofprogesteronebysyncytiotrophoblastandestrogensbyfetoplacentalunit.Intervillous space (Maternal) Sycytiotrophoblast Cholesterol pregnenolone Fetal zone adrenal cortex Pregnenolone Pregnenolone-s 17OH-Pregnenolone-s Sulfo-Transferase CYP11A1 Star-related protein CYP11A1 Star protein CYP17 (Hydroxylase) CYP17 (17/20 lyase) ACTH Cholesterol Fetal pituitary CYP19 Aromatase E3 E2 E1 CYP19 Aromatase Sulfatase 16OH DHEA 16OH A'DIONE 16OH T Progesterone 16OH DHEAS DHEAS DHEAS DHEAS DHEAS16OH DHEAS Fetal liver DHEA A'DIONE T 3˜HSD 3˜HSD 17˜HSD Actions in maternal compartment Actions in maternal compartment Peripheral conversion to E2 MC2R
Progesterone is released primarily into the maternal circulation and is required for implantation and maintenance of pregnancy. Progesterone also has several effects on maternal physiology and induces breast growth and differentiation. The switch from corpus luteum–derived progesterone to placental-derived progesterone (referred to as the luteal-placental shift) is complete at about the eighth week of pregnancy. Progesterone (and pregnenolone) are used by the transitional zone of the fetal cortex to make cortisol late in pregnancy.
Estrogens are also produced by syncytiotrophoblasts. Syncytiotrophoblasts are similar to ovarian granulosa cells in that they lack CYP17 and are dependent on another cell type to provide 19-carbon androgens for aromatization (see
Fig.
44.35 ). The ancillary androgen-producing cells reside in the fetal adrenal cortex.
The fetal adrenal cortex contains an outer definitive zone, a middle transitional zone, and an inner fetal zone. The definitive and transitional zones give rise to the zona glomerulosa and zona fasciculata, respectively. Aldosterone synthesis is initiated close to parturition. Synthesis of cortisol begins at about 6 months and increases during late gestation. The fetal zone is the predominant portion of the adrenal cortex in the fetus; it constitutes as much as 80% of the bulk of the large fetal adrenal and is the site of most fetal adrenal steroidogenesis. The fetal zone strongly resembles the zona reticularis in that it expresses little or no 3β-HSD (see